New gene for Alzheimer’s risk identified
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esearchers have identified a genetic variation that may indicate an increased risk for late-onset Alzheimer’s disease. The finding is a result of a collaboration between deCODE genetics in Iceland and Emory Alzheimer’s researchers. They read the entire genomes of 2,261 Icelanders. The new variant increases risk by about a factor of three, an effect that is similar in scope to that of the most common genetic risk factor for Alzheimer’s, ApoE E4. However, the new variant, called TREM2, is rarer: it is found in one in every 160 people in Iceland, compared with more than 17%
of the Icelandic population for ApoE E4, a percentage that is higher in other countries. People who carry the variation and do develop Alzheimer’s disease do so roughly three years earlier than non-carriers. Although rare, the variant is important because it adds to a growing list of genes linked to Alzheimer’s disease, and it provides clues to causal mechanisms. “First, the results demonstrate that certain rare genetic variants can have a strong influence on Alzheimer’s disease risk for individuals carrying those variants,” says Allan Levey, director of Emory’s Alzheimer’s Disease Research Center and chair of neurology. “Second, since the TREM2 gene is expressed in microglia and other immune cells where it triggers production of inflammatory cytokines, the finding provides growing evidence that chronic inflammation is relevant for the development of the disease, and that modulating TREM2 signaling and microglial function is a potential therapeutic strategy.”
Targeting inflammation to treat depression
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esearchers at Emory have found that a medication that inhibits inflammation may offer promise for people with difficult-totreat depression. Prior studies have suggested that depressed people with evidence of high inflammation are less likely to respond to anti-depressant medications and psychotherapy. This study was designed to see whether blocking inflammation would be a useful treatment for people with difficultto-treat depression or only those with high levels of inflammation. The study employed infliximab, used to treat autoimmune and inflammatory diseases such as rheumatoid arthritis and inflammatory bowel disease. Infliximab blocks tumor necrosis factor, a key
molecule in inflammation that has been shown to be elevated in some depressed people. Study participants all had major depression and were moderately resistant to conventional antidepressant treatment. Each participant was assigned either to infliximab or to a non-active placebo treatment. When investigators looked at the results for the group as a whole, no significant differences were found in the improvement of depression symptoms between the drug and placebo groups. However, when the subjects with high inflammation were examined separately, they exhibited a much better response to infliximab than to the placebo. Inflammation in this study was measured using a simple blood test that is readily available and measures
C-reactive protein. “The prediction of an antidepressant response using a simple blood test is one of the holy grails in psychiatry,” says Andrew Miller, senior author of the study and the Timmie Professor of Psychiatry and Behavioral Sciences. “This is especially important because the blood test not only measured what we think is the root cause of depression in these patients but also is the target of the drug.” SP R I N G 2013 7